The investigator will attempt to introduce relevant HIV genes into the germline of mice with the intent of deriving transgenic animals which will serve as appropriate models for the study of mechanisms of HIV pathogenesis. The author has four specific aims, the first of which is to define the role(s) of the HIV regulatory genes, tat and nef, in inducing pathogenesis by introducing each of them individually, or in combination, into the germline of mice. The second goal is to target specific HIV regulatory genes, particularly the tat gene, to restricted cell types in mice by the use of tissue-specific transcriptional control elements in order to enhance the detection of anticipated disease phenotypes. The third goal is to try to understand the mechanism of HIV latency and activation as it pertains to the interaction between the viral LTR (long terminal repeat) and viral and cellular trans-activators. Lastly, the investigator proposes to ascertain the importance of environmental factors, particularly other human viruses (such as JC virus and human hepatitis B virus), in inducing HIV pathogenesis in transgenic mice.